Powerpoint presentation providing evidence linking the gut microbiota to aspects of sleep behavior via microbiota-gut-brain axis pathways.

1. Role of the Gut Microbiome in Sleep Health
Jonathan Lendrum
Department of Biology, University of Wisconsin-La Crosse, La Crosse, WI 54601
Correspondence: Lendrum.jona@uwlax.edu 1

2. Why do we spend 1/3 of our lives asleep? Why is
there such a large variation in sleep requirements?
2

3. Santiago Ramon’s 1895 Sleep Hypothesis
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The great neuroscientist Santiago Ramón y Cajal (1852–
1934) studied neurons extensively and, also, glial cells —
astrocytes in particular. Based on his observation that
the length of astrocytic processes varies greatly between
cells, he imagined that astrocytes dynamically extend
and retract their processes. He hypothesized, in 1895,
that: (1) during sleep, endfeet of astrocytes invade the
synaptic cleft to serve as a ‘circuit breaker’, pausing
synaptic transmission and (2) during wakefulness, those
endfeet retract, restoring synaptic transmission.

4. 4
(2013)
There are approximately 90 billion neurons in the brain that
consume nearly 25% of the bodies total energy demand.
BRAIN (CNS)
• 2% of body weight (3 pounds)
• 15% of cardiac output
• 20% total O2 consumption
• 25% total glucose consumption
All biological activity is
associated with production of
waste products (escaped NTs).
Does the brain really recycle all
cellular waste products?

5. An intercellular “glymphatic” (g- glial mediated)
pathway uses cerebrospinal fluid to clear cell waste
from the brain during sleep phases and may reveal
new targets for treating neurodegenerative diseases.
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AQP4 deletion suppresses clearance of beta-amyloid by 60%
Norepinephrine (NE) regulates cortical neuronal activity and the volume of the interstitial space.

6. 6

7. 7

8. Gut Microbiome- The Forgotten Endocrine Organ
Microbiota is the coevolved ecological community of
commensal, symbiotic and pathogenic microorganisms
that literally share our body space.
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Gut-Microbiome
• Trains Immune System
• Suppresses Pathogens
• Synthesizes Vitamins (K)
• Main Source of SCFAs
• Ferments Carbohydrates
• Maintains Gut Barrier
• Regulates Brain and Gut-
-Development ( gene pool)

9. Microbiota-Gut-Brain-(Sleep?) Axis

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Bacteroides (5x)- Animal protein/fat
Despite the clock-like
nature of microbiome
diversification in African
apes, the gut
microbiomes of humans
have undergone an
accelerated rate of
change and are more
different form those of
each wild ape population
than expected based on
the evolutionary time
separating Homo from
Pan and Gorilla.
Sleep Intensity Hypothesis

12. Thesis
• My review argued that the gut microbiome and human
sleep behavior coevolved with one another to maximize
net energy conservation while maintaining optimal
niche exploitation.
• The gut microbiome provides a pathway for optimal
energy acquisition and sleep regulation (somnogenic
peptides, etc).
• Alternatively, sleep provides the pathway for optimal
energy conservation (convective waste clearance).
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13. 13
Experimental Design
Harlan T.D. 08806i Low Fat (10% kcal) Diet

14. 14
Experimental Design
Day: 6am/6pm
Night: 6pm/6am Record Sleep/Wake Behavior
Cages Fit With Infrared Cameras

15. Results- Highlights
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16. Results- Broad-Spectrum Antibiotic Gavage Induces
Intestinal Dysbiosis
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Antibiotic
Control
**
Illumina Next Generation Sequencing 16s rRNA (V2-V3 region), Bioinformatics QIIME

17. Results- Perturbation of Gut Microbiota Increases
Intestinal Permeability and Colonic Secretion
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**

18. Results- Antibiotic Gavage Mimics Germ-Free Phenotype
• Enlarged Caecum
• Loss of mucosal architecture
• Expansion of lamina propria
• Enterocyte hyperplasia
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Control Caecum Antibiotic Caecum

19. Results- Antibiotic-Induced Dysbiosis Alters Intestinal
Motility, Immune Homeostasis and Fecal Gross Energy
Content
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**
**
** **
**
**
Impaired Immune State
Altered Gut Function
Shifted Metabolic State

20. Perturbation of Gut Microbiota Alters Sleep Architecture
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0
10
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30
40
50
60
70
80
90
7-9am 9-11am 11-1pm 1-3pm 3-5pm 5-7pm 7-9pm 9-11pm 11-1am 1-3am 3-5am 5-7am
Mean%ofSleep
Control Antibiotic
Light Dark
Figure 5. 24-hour sleep profile of antibiotic treated animals exhibits a statistically significant reduction in the mean % of
sleep during the dark phase of day (6pm-6am). Paired sample t-tests were analyzed for light and dark phases separately.
The dark phase p-value <0.01** with a 14.2% difference of means.

21. Conclusions
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The results of this study suggest that broad-spectrum antibiotic-induced reduces gastrointestinal
motility, enhances colonic ion secretion, impairs mucosal barrier function, reduces energy harvest
capacity, alters sleep architecture and may contribute to congruent neurological and
gastrointestinal disorders via microbiota-gut-brain axis pathways.

22. Thesis Conclusions
• Through evolutionary adaptation of temporal cycling
of sleep/wake behavior, we are able to
compartmentalize important physiological processes
over time. This allows for certain physiological
processes to maximize their efficiency by not
interfering with contradicting processes at the same
time (futile cycling). Sleep wake/ cycling down
regulates specific biological processes in waking and
up regulates them in sleep, thereby decreasing
energy demands imposed by wakefulness, reducing
cellular infrastructure requirements, and resulting in
overall energy conservation.
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23. Acknowledgments
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Supported by: NIH R15 DK097460-01A1 (SL) and UW-L undergraduate research
grant (JL). The authors thank the University of Wisconsin-Biotechnology Center
DNA Sequencing Facility for providing sequencing and bioinformatics services.
• Dr. Bradley Seebach- Neurophysiologist
• Dr. Sumei Liu- Gastroenterologist
• Dr. Barrett Klein- Sleep Expert
• Dr. Andrew Berns- Computer Science Sleep Analysis

24. 24
QUESTIONS?
Jonathan Lendrum
Department of Biology, University of Wisconsin-La Crosse, La Crosse, WI 54601
Correspondence: Lendrum.jona@uwlax.edu

25. Role of the Gut Microbiome in Sleep Health
Jonathan Lendrum
Department of Biology, University of Wisconsin-La Crosse, La Crosse, WI 54601
Correspondence: Lendrum.jona@uwlax.edu 25
QUESTIONS?